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Scientifica
Volume 2013, Article ID 750871, 17 pages
http://dx.doi.org/10.1155/2013/750871
Review Article

Mammalian Tribbles Homologs at the Crossroads of Endoplasmic Reticulum Stress and Mammalian Target of Rapamycin Pathways

1Research Service and Division of Nephrology-Hypertension, Veterans Affairs San Diego Healthcare System, Veterans Medical Research Foundation, Mail Code 151, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
2Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA

Received 7 October 2013; Accepted 20 November 2013

Academic Editors: F. Artunc, J. L. Barnes, and G.-P. Zhou

Copyright © 2013 Robyn Cunard. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease.